Multidrug resistance phenotype in high grade soft tissue sarcoma: Correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy

Rafael E Jimenez, Mark M. Zalupski, John J. Frank, Wei Du, James R. Ryan, David R. Lucas

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

BACKGROUND. P-glycoprotein-mediated drug efflux has been implicated as an important mechanism of multidrug resistance (MDR) in cancer. Its role in chemotherapy resistance in soft tissue sarcoma is unclear. METHODS. Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and ISB-1) that recognize different epitopes of P-glycoprotein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = moderate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with both antibodies were considered MDR positive. The resection specimens were evaluated for tumor necrosis postchemotherapy. Pathologic response was graded as good for <15%, moderate for 15-50%, or poor for >50% posttreatment tumor viability. RESULTS. Of the 29 pretreatment specimens, 10 (34%) were MDR positive and 19 (66%) were MDR negative. Pathologic response to treatment was characterized as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positive biopsies, 9 (90%) had poor response, compared with 7 (36%) in the MDR negative biopsy group (P = 0.0078). None of the cases with MDR positive biopsies had a good response, compared with 6 cases in which biopsies were MDR negative (32%) (P = 0.057). Only one MDR negative case became MDR positive posttreatment. CONCLUSIONS. Expression of MDR phenotype is found in approximately one-third of high grade soft tissue sarcomas. These preliminary data show a significant correlation between MDR phenotype and poor pathologic response to chemotherapy, and suggest that MDR induction by chemotherapy in soft tissue sarcoma is an uncommon event.

Original languageEnglish (US)
Pages (from-to)976-981
Number of pages6
JournalCancer
Volume86
Issue number6
DOIs
StatePublished - Sep 15 1999
Externally publishedYes

Fingerprint

Multiple Drug Resistance
P-Glycoprotein
Sarcoma
Immunohistochemistry
Phenotype
Drug Therapy
Biopsy
Neoplasms
Staining and Labeling
Induction Chemotherapy
Epitopes
Necrosis
Monoclonal Antibodies

Keywords

  • C494
  • Chemoresistance
  • Chemotherapy
  • JSB- 1
  • MDR
  • P-glycoprotein
  • Soft tissue sarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Multidrug resistance phenotype in high grade soft tissue sarcoma : Correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy. / Jimenez, Rafael E; Zalupski, Mark M.; Frank, John J.; Du, Wei; Ryan, James R.; Lucas, David R.

In: Cancer, Vol. 86, No. 6, 15.09.1999, p. 976-981.

Research output: Contribution to journalArticle

Jimenez, Rafael E ; Zalupski, Mark M. ; Frank, John J. ; Du, Wei ; Ryan, James R. ; Lucas, David R. / Multidrug resistance phenotype in high grade soft tissue sarcoma : Correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy. In: Cancer. 1999 ; Vol. 86, No. 6. pp. 976-981.
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abstract = "BACKGROUND. P-glycoprotein-mediated drug efflux has been implicated as an important mechanism of multidrug resistance (MDR) in cancer. Its role in chemotherapy resistance in soft tissue sarcoma is unclear. METHODS. Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and ISB-1) that recognize different epitopes of P-glycoprotein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = moderate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with both antibodies were considered MDR positive. The resection specimens were evaluated for tumor necrosis postchemotherapy. Pathologic response was graded as good for <15{\%}, moderate for 15-50{\%}, or poor for >50{\%} posttreatment tumor viability. RESULTS. Of the 29 pretreatment specimens, 10 (34{\%}) were MDR positive and 19 (66{\%}) were MDR negative. Pathologic response to treatment was characterized as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positive biopsies, 9 (90{\%}) had poor response, compared with 7 (36{\%}) in the MDR negative biopsy group (P = 0.0078). None of the cases with MDR positive biopsies had a good response, compared with 6 cases in which biopsies were MDR negative (32{\%}) (P = 0.057). Only one MDR negative case became MDR positive posttreatment. CONCLUSIONS. Expression of MDR phenotype is found in approximately one-third of high grade soft tissue sarcomas. These preliminary data show a significant correlation between MDR phenotype and poor pathologic response to chemotherapy, and suggest that MDR induction by chemotherapy in soft tissue sarcoma is an uncommon event.",
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T1 - Multidrug resistance phenotype in high grade soft tissue sarcoma

T2 - Correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy

AU - Jimenez, Rafael E

AU - Zalupski, Mark M.

AU - Frank, John J.

AU - Du, Wei

AU - Ryan, James R.

AU - Lucas, David R.

PY - 1999/9/15

Y1 - 1999/9/15

N2 - BACKGROUND. P-glycoprotein-mediated drug efflux has been implicated as an important mechanism of multidrug resistance (MDR) in cancer. Its role in chemotherapy resistance in soft tissue sarcoma is unclear. METHODS. Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and ISB-1) that recognize different epitopes of P-glycoprotein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = moderate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with both antibodies were considered MDR positive. The resection specimens were evaluated for tumor necrosis postchemotherapy. Pathologic response was graded as good for <15%, moderate for 15-50%, or poor for >50% posttreatment tumor viability. RESULTS. Of the 29 pretreatment specimens, 10 (34%) were MDR positive and 19 (66%) were MDR negative. Pathologic response to treatment was characterized as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positive biopsies, 9 (90%) had poor response, compared with 7 (36%) in the MDR negative biopsy group (P = 0.0078). None of the cases with MDR positive biopsies had a good response, compared with 6 cases in which biopsies were MDR negative (32%) (P = 0.057). Only one MDR negative case became MDR positive posttreatment. CONCLUSIONS. Expression of MDR phenotype is found in approximately one-third of high grade soft tissue sarcomas. These preliminary data show a significant correlation between MDR phenotype and poor pathologic response to chemotherapy, and suggest that MDR induction by chemotherapy in soft tissue sarcoma is an uncommon event.

AB - BACKGROUND. P-glycoprotein-mediated drug efflux has been implicated as an important mechanism of multidrug resistance (MDR) in cancer. Its role in chemotherapy resistance in soft tissue sarcoma is unclear. METHODS. Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and ISB-1) that recognize different epitopes of P-glycoprotein. Staining intensity was graded 0 = negative, 1 = equivocal, 2 = moderate, 3 = strong. Only cases with Grade 2 or 3 staining intensity with both antibodies were considered MDR positive. The resection specimens were evaluated for tumor necrosis postchemotherapy. Pathologic response was graded as good for <15%, moderate for 15-50%, or poor for >50% posttreatment tumor viability. RESULTS. Of the 29 pretreatment specimens, 10 (34%) were MDR positive and 19 (66%) were MDR negative. Pathologic response to treatment was characterized as good in 6, moderate in 7, and poor in 16 patients. Of the MDR positive biopsies, 9 (90%) had poor response, compared with 7 (36%) in the MDR negative biopsy group (P = 0.0078). None of the cases with MDR positive biopsies had a good response, compared with 6 cases in which biopsies were MDR negative (32%) (P = 0.057). Only one MDR negative case became MDR positive posttreatment. CONCLUSIONS. Expression of MDR phenotype is found in approximately one-third of high grade soft tissue sarcomas. These preliminary data show a significant correlation between MDR phenotype and poor pathologic response to chemotherapy, and suggest that MDR induction by chemotherapy in soft tissue sarcoma is an uncommon event.

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KW - Chemoresistance

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KW - JSB- 1

KW - MDR

KW - P-glycoprotein

KW - Soft tissue sarcoma

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